On February 24, 2022 A Columbus pharmaceutical reported that has raised $40 million toward a drug that could slow progression of a type of treatment-resistant metastatic breast cancer – all because a grad student at Duke University five years ago happened to grab a vial of the once-abandoned osteoporosis treatment (Press release, Sermonix Pharmaceuticals, FEB 24, 2022, View Source [SID1234608988]).

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Sermonix Pharmaceuticals Inc. is awaiting data from more than 100 patients treated over the past two years. If results show significant benefit, the company could seek a meeting this summer with the U.S. Food and Drug Administration to map out next steps, COO Dr. Miriam Portman said.

The company licensed the drug lasofoxifene in 2015 to renew efforts toward approval as an osteoporosis treatment, but quickly changed purpose when Duke identified potential in breast cancer. That use has since shown promising results in mice. The FDA granted fast-track status to the study in 2019.

"It was really an ‘aha moment’ and a huge pivot point for us," said Dr. David Portman, Sermonix CEO. "The company is confident in the activity of the drug, and is hopeful to get breakthrough designation and get the drug to availability to patients in the coming years."

Perceptive Xontogeny Ventures led the Series A3 round in November with some repeat investors. Perceptive partners Fred Callori and Ben Askew joined the Sermonix board. The company previously raised seed funding and a $20 million round in 2019.

Sermonix plans to open a downtown office this spring, and some Philadelphia-area executives with pharmaceutical industry experience plan to move, David Portman said. The funding will help it wrap up the two clinical trials, pursue regulatory approval and increase manufacturing of both the drug and a companion diagnostic test for the type of cancer it targets.

The Portmans, physicians who are married and live in Bexley, founded Columbus Center for Women’s Health Research in 1997 to conduct clinical studies on hormone therapy, osteoporosis, contraception and heart disease. It was acquired by another Columbus research business in 2015. They formed Sermonix and licensed lasofoxifene from Ligand Pharmaceuticals Inc.

San Diego-based Ligand developed the drug in a collaboration with Pfizer Inc. in the 1990s. The hormonal therapy is a selective estrogen receptor modulator (or SERM, hence Sermonix) – basically fooling estrogen receptors to slow diseases stimulated by the hormone. But attempts at FDA approval hit a road block in 2009, and Pfizer went with a different compound. Rights later reverted to Ligand.

Sermonix’s license entitles Ligand to as much as $45 million in milestone payments and 6% to 10% royalties on any eventual sales, according to regulatory filings.

Meanwhile, Donald McDonnell, who was on the inventing team at Ligand before moving to Duke, had become co‐director of Duke Cancer Institute’s program in women’s cancer.

Treatments that inhibit the production or uptake of estrogen are effective against types of breast tumors stimulated by the hormone – but those tumors often mutate to resist the therapy.

Researchers in McDonnell’s lab in 2016 were studying a specific mutation that’s diagnosed in about 20,000 patients a year. A graduate student was working with ovarian tumor cells with the same mutation, and started testing every known hormonal treatment on them, according to the institute’s website.

Lasofoxifene – on hand only because of McDonnell’s Ligand work – was the only one that slowed growth.

"He had some of that compound on his shelf," David Portman said. "It showed very unexpected activity. It was a fortunate series of events."

Duke patented the application for breast cancer, and started working with Sermonix, the license-holder, toward commercialization. The company has a video explaining how it works.

"That was a significant unmet medical need and a far greater medical benefit to patients than what we were currently working on," David Portman said.

Because of the earlier osteoporosis studies, the drug could skip over the first phase showing it’s safe for use in humans. Two trials are wrapping up comparing the current standard of care for treatment-resistant cancer against lasofoxifene; one uses it alone and the other in combination with a second drug.

Breast cancer with this mutation is incurable once at this stage, but the therapy aims to slow progression and spread, making it a manageable chronic condition.

Perceptive Xontogeny, a joint fund of New York City and Boston firms, also was the lead investor in the $40 million 2020 round that launched Grove City gene therapy startup Forge Biologics Inc., part of a fast-growing Central Ohio biotech sector.

"It felt very lonely for a while, and now it’s started to grow significantly," David Portman said. "It is becoming an exciting hub."

On February 24, 2022 Novocure (NASDAQ: NVCR) reported that a new study published in the Journal of Clinical Investigation (JCI) finds treatment with Tumor Treating Fields (TTFields) mediated cell disruption activates the immune system and triggers an anti-tumor cell response that may be effectively used together with existing immunotherapy approaches in the treatment of solid tumors, with limited systemic toxicity (Press release, NovoCure, FEB 24, 2022, View Source [SID1234609006]).

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"TTFields’ ability to activate a downstream immune response, effectively turning a cold tumor hot, is a unique element of TTFields therapy," said Uri Weinberg, Novocure’s Chief Science Officer. "Given the depth of clinical research focused on the use of immunotherapies and the broad applicability of TTFields, this could be critical to the treatment path for solid tumor cancers."

Preclinical research has shown evidence that TTFields may induce a pro-inflammatory and broader immunological effect on tumor cells. This study outlines translational research by Dr. Dongjiang Chen and colleagues from the David Tran Laboratory of Quantitative Cancer Research at the University of Florida. Preclinical data demonstrated that treatment with TTFields directly disrupted the nuclear envelope of glioblastoma (GBM) tumor cells. This led to leakage of DNA that activates the cGAS/STING and AIM2 signaling pathways, driving early anti-tumor immune responses. Further, a genetic signature was identified in patients treated with TTFields therapy indicating an acquired immune response. Collectively, these novel preclinical and patient data further elucidate the downstream cellular processes resulting from TTFields’ mechanism of action that support the potential for a therapeutic advantage when used together with immunotherapy, with limited systemic toxicity.

Based on these findings, Dr. David Tran, Chief of the Division of Neuro-Oncology, at the McKnight Brain Institute at the University of Florida, designed the phase 2 pilot 2-THE-TOP clinical study, evaluating the use of TTFields therapy together with the anti-PD-1 therapy (pembrolizumab) and chemotherapy (temozolomide) for the treatment of newly diagnosed GBM in 25 patients. In November 2021, updated data from the ongoing 2-THE-TOP study was presented at the Society for Neuro-Oncology (SNO) 2021 Annual Meeting. These preliminary data showed 19 patients with greater than 9 months of follow-up displayed a median progression-free survival (primary endpoint) of at least 11.2 months. Additionally, 193,760 peripheral blood mononuclear cells were sequenced in 12 patients before pembrolizumab was administered and detected robust post-TTFields T cell activation in 11 of 12 patients via the T1IFN trajectory with a strong correlation with the TCRαβ clonal expansion Simpson index (Spearman coefficient r=-0.8, P=0.014). This finding is in line with the JCI publication, and contributes to the building body of evidence suggesting TTFields’ mechanism of action induces a downstream signaling pathway that initiates an active immune response that aids the body’s ability to fight cancer cells.

About Tumor Treating Fields

Tumor Treating Fields, or TTFields, are electric fields that disrupt cancer cell division. Fundamental scientific research extends across more than two decades and, in all preclinical research to date, TTFields have demonstrated a consistent anti-mitotic effect. TTFields therapy is intended principally for use together with other standard-of-care cancer treatments. There is a growing body of evidence that supports TTFields’ broad applicability with certain other cancer therapies, including radiation therapy, certain chemotherapies and certain immunotherapies. In clinical research and commercial experience to date, TTFields therapy has exhibited no systemic toxicity, with mild to moderate skin irritation being the most common side effect. The TTFields global development program includes a network of preclinical collaborators and a broad range of clinical trials across all phases, including four phase 3 pivotal trials in a variety of tumor types. To date, more than 22,000 patients have been treated with TTFields therapy.

On February 24, 2022 Portage Biotech Inc. (NASDAQ: PRTG) ("Portage" or the "Company"), a clinical-stage immuno-oncology company developing therapies to improve patient lives and increase survival by avoiding and overcoming cancer treatment resistance, reported financial results for the quarter ended December 31, 2021 (the "third quarter") (Press release, Portage Biotech, FEB 24, 2022, View Source [SID1234609033]).

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"During the third quarter and in recent weeks we’ve taken steps to accelerate our lead programs for PORT-2 and PORT-3, investigating options to expand our clinical sites beyond our current footprint and finding the means of accelerating patient enrollment," said Dr. Ian Walters, chief executive officer of Portage. "With our enhanced management team, efficient organization, and financial resources obtained in 2021, we are well positioned to execute our unique drug development strategy to deliver on important clinical milestones over the next two years."

Business Update

Enhanced the management team with the appointments of Brian Wiley as Chief Business Officer, Joseph Ciavarella as Chief Accounting Officer; expanded the Board of Directors with the addition of Jim Mellon, Linda Kozick, and Mark Simon.
Enrollment continues in the Company’s IMP-MEL randomized Phase 1/2 study of PORT-2 and its PRECIOUS Phase 1 study of PORT-3 in patients with NY-ESO-1 expressing tumors.
The Company plans to issue a Research & Development update in March 2022 which will include preliminary safety data on its PORT-2 and PORT-3 programs as well as other details from its clinical development plan.
Presented at high-profile investor conferences:
Management participated in January 2022 investor conferences including the LifeSci Advisors Corporate Access Event, H.C. Wainwright BioConnect Conference, and the B. Riley Securities’ Oncology Investor Conference.
Hosted Key Opinion Webinar How iNKT Agonists Could Improve Immuno-Oncology Treatment with leading researchers from La Jolla Institute of Immunology and Imperial College London. Replay available here.
Third Quarter FY 2022 Financial Results

The Company generated a net loss and comprehensive loss of approximately $4.2 million in the three months ended December 31, 2021 ("Fiscal 2022 Quarter"), compared to a net loss and comprehensive loss of approximately $1.3 million in the three months ended December 31, 2020 ("Fiscal 2021 Quarter"), an increase in loss of $2.9 million year over year. Operating expenses, which include research and development and general and administrative expenses, were approximately $4.2 million in the Fiscal 2022 Quarter, compared to $0.9 million in the Fiscal 2021 Quarter, an increase of $3.3 million, which is discussed more fully below.

The Company’s other items of income and expense were substantially non-cash in nature and were approximately $0.1 million net income in the Fiscal 2022 Quarter, compared to approximately $0.5 million net loss in the Fiscal 2021 Quarter, a change in other items of income and expense of approximately $0.6 million, year over year. The primary reasons for the year over year difference in other items of income and expense was the change of $0.8 million in the fair value of the warrants issued with respect to the SalvaRx note settlement, which was partially offset by the year over year increase in the loss from an associate accounted for under the equity method of $0.1 million and the income on equity issued at a discount of $0.1 million in the Fiscal 2021 Quarter, representing the difference between the market price and the contractual exercise price, relating to the settlement of the SalvaRx notes and warrants.

Research & development ("R&D") costs increased by approximately $1.5 million, from approximately $0.4 million during the Fiscal 2021 Quarter, to approximately $1.9 million during the Fiscal 2022 Quarter. The increase was primarily attributable to non-cash share-based compensation expense associated with grants made under the 2021 Equity Incentive Plan of $1.0 million and salaries and bonuses of $0.7 million to directors and senior management. Additionally, the Fiscal 2021 Quarter was impacted by a general slow down in expenditures resulting from the pandemic.

General and administrative ("G&A") expenses increased by approximately $1.8 million, from approximately $0.4 million during the Fiscal 2021 Quarter, to approximately $2.2 million during the Fiscal 2022 Quarter. The principal reason for the increase in the Fiscal 2022 Quarter was the $1.1 million of non-cash share-based compensation expense associated with the Company’s 2021 Equity Incentive Plan, of which $0.7 million is associated with Directors’ compensation, and $0.4 million is associated with management compensation. No share-based compensation expense under the 2021 Equity Incentive Plan was incurred during the Fiscal 2021 Quarter. Additionally, the Company incurred an increase of $0.4 million in professional fees relating to initiatives associated with a corporate restructuring and public relations / business development. Finally, D&O insurance premiums increased $0.4 million in the current year period due to market rate increases in the cost of coverage.

Additionally, the Company reflected a net income tax expense of approximately $0.1 million in the Fiscal 2022 Quarter, compared to a net income tax benefit of approximately $0.1 million in the Fiscal 2021 Quarter. The Fiscal 2022 Quarter reflects the change in the foreign currency exchange rate on deferred tax liability settleable in British pounds sterling and the Fiscal 2021 Quarter reflected recoverable research and development tax credits generated in the U.K.

As of December 31, 2021, the Company had cash and cash equivalents of approximately $25.6 million and total current liabilities of approximately $0.6 million (inclusive of approximately $0.2 million warrant liability settleable on a non-cash basis). For the nine months ended December 31, 2021, the Company is reporting a net loss of approximately $10.3 million and cash used in operating activities of approximately $4.5 million. As of January 31, 2022, the Company had approximately $25.1 million of cash on hand to enable achieving important clinical milestones over the next two years.

On February 24, 2022 EVERSANA reported that it will be attending Reuters Events: Pharma USA 2022 on March 16th & 17th in Philadelphia (Press release, EVERSANA, FEB 24, 2022, View Source [SID1234609061]). Krista Pinto, President, Deployment Solutions, will participate with industry leaders in a panel discussion covering the importance of salesforce instances keeping pace with rapidly evolving HCP preferences March 17th at 12:20 PM EST . Key topics include:

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With a shift in HCP preferences, expectations and a hybrid future, learn how to maximize your salesforce outputs by shifting the way your organization sets KPI’s as well as the metrics used to read them
New methods to provide value to your HCPs in virtual calls
Learn how to match HCP preferences with sales rep interactions to leave long-lasting impressions that lead to conversions
How can we you empower the digital rep experience from a service orientation perspective?
Confirmed speakers:

Krista Pinto, President, Deployment Solutions, EVERSANA
Dion Warren, VP, Head of U.S. Oncology Business Unit, Takeda
Frank Armenante, Director, Commercial Execution, Novo Nordisk
Tatiana Yglesias, Head of Migraine Marketing, Neuroscience, Novartis
Nithya Srinivasan, Director of Marketing, Rheumatology, Janssen
Pharma USA unites North America’s visionary pharma changemakers, leading solution providers, patient experts and industry heavyweights — from commercial, marketing, medical affairs, patient engagement, market access and RWE — who’ll unlock unrestrained innovation and drastically improved health outcomes.

On February 24, 2022 Aclaris Therapeutics, Inc. (NASDAQ: ACRS), a clinical-stage biopharmaceutical company focused on developing novel drug candidates for immuno-inflammatory diseases, reported its financial results for the fourth quarter and full year of 2021 and provided a corporate update (Press release, Aclaris Therapeutics, FEB 24, 2022, View Source [SID1234608927]).

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"2021 was a tremendous year for the progression of our drug development pipeline, and I’m very proud of what our team has accomplished," said Dr. Neal Walker, President & CEO of Aclaris. "We reported positive data for our Phase 2a trials of zunsemetinib in subjects with moderate to severe rheumatoid arthritis (RA) and ATI-1777 in subjects with moderate to severe atopic dermatitis (AD), and strengthened our balance sheet to continue this momentum in 2022. Moving forward, we are progressing zunsemetinib in three immuno-inflammatory indications, moving ATI-1777 forward in moderate to severe AD, and progressing ATI-2138 in SAD/MAD studies. Our KINect drug discovery platform continues to be productive and we now have three clinical-stage compounds as well as an early-stage immuno-inflammatory and oncology pipeline. We have the privilege of working toward the goal of helping address the needs of patients with immuno-inflammatory diseases as well as cancer and look forward to progressing our assets to achieve this goal."

Research and Development Highlights:

The global COVID-19 pandemic continues to rapidly evolve and has caused and may continue to cause Aclaris to experience disruptions that could impact the timing of its research and development and regulatory activities listed below.

Clinical Programs

Zunsemetinib, an investigational oral small molecule MK2 inhibitor:
Currently being developed as a potential treatment for immuno-inflammatory diseases
ATI-450-RA-202: This Phase 2b dose ranging trial to investigate the efficacy, safety, tolerability, pharmacokinetics and pharmacodynamics of multiple doses (20 mg and 50 mg twice daily) of zunsemetinib in combination with methotrexate in subjects with moderate to severe RA is ongoing.
Aclaris anticipates increasing the size of the patient population from approximately 195 to approximately 240 subjects and expects topline data in 2023.
ATI-450-HS-201: This Phase 2a trial to investigate the efficacy, safety, tolerability, pharmacokinetics and pharmacodynamics of zunsemetinib (50 mg twice daily) in subjects with moderate to severe HS is ongoing.
Aclaris expects topline data in the first half of 2023.
ATI-450-PsA-201: Aclaris plans to progress zunsemetinib (50 mg twice daily) into a Phase 2a trial in subjects with moderate to severe psoriatic arthritis in the first half of 2022.
ATI-1777, an investigational topical "soft" Janus kinase (JAK) 1/3 inhibitor:
Currently being developing as a potential treatment for moderate to severe AD
Aclaris plans to progress ATI-1777 into a Phase 2b trial in subjects with moderate to severe AD in the first half of 2022. In this trial, Aclaris plans to explore multiple concentrations of twice daily treatment with ATI-1777 and a single concentration of once daily treatment with ATI-1777, in patients 12 years and older.
ATI-2138, an investigational oral ITK/TXK/JAK3 (ITJ) inhibitor:
Currently being developed as a potential treatment for T cell-mediated autoimmune diseases
ATI-2138-PKPD-101: This Phase 1 single ascending dose (SAD) trial to investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of ATI-2138 in healthy subjects is ongoing.
Aclaris expects topline data in 2022.
If the Phase 1 SAD trial is successful, Aclaris currently plans to initiate a two-week Phase 1 multiple ascending dose trial of ATI-2138 in subjects with psoriasis in 2022. Aclaris is also currently exploring alternative indications to the planned indication that are relevant to the mechanism of action.
Preclinical Programs

ATI-2231, an investigational oral MK2 inhibitor compound:
Currently being explored as a potential treatment for pancreatic cancer and metastatic breast cancer as well as in preventing bone loss in patients with metastatic breast cancer
Second MK2 inhibitor generated from Aclaris’ proprietary KINect drug discovery platform and designed to have a long half-life.
IND-enabling studies are underway, and Aclaris expects to submit an IND by the end of 2022.
Discovery Programs

Currently developing oral gut-biased JAK inhibitors with limited systemic exposure as potential treatments for inflammatory bowel disease.
Central nervous system (CNS) kinase inhibitor targets:
Currently engaged in research to identify brain penetrant kinase inhibitor candidates and assess their impact on neuronal pro-inflammatory cytokine production, microglia growth and survival, and neurodegeneration.
Other Highlights:

James Loerop appointed as Chief Business Officer in January 2022.
Aclaris plans to hire additional key leadership positions over the coming months to support its operational plans and strategic direction.
Financial Highlights:

Liquidity and Capital Resources

As of December 31, 2021, Aclaris had aggregate cash, cash equivalents and marketable securities of $225.7 million compared to $54.1 million as of December 31, 2020. The primary factors for the change in cash, cash equivalents and marketable securities during the year ended December 31, 2021 included:

Net cash used in operating activities of $52.1 million. This amount was comprised of the following:
$90.9 million net loss
$1.3 million cash used from changes in operating assets and liabilities
$24.3 million of non-cash charges for the revaluation of contingent consideration
$14.1 million of non-cash stock-based compensation expense
$1.7 million of other non-cash charges
Net cash used to repay outstanding debt and fees of $11.5 million in July 2021.
Aggregate net proceeds of $238.2 million from public offerings in January 2021 and June 2021 in which Aclaris sold a total of 14.4 million shares of common stock.
Aclaris anticipates that its cash, cash equivalents and marketable securities as of December 31, 2021 will be sufficient to fund its operations through the end of 2024, without giving effect to any potential business development transactions or financing activities.

Financial Results

Fourth Quarter 2021

Net loss was $22.8 million for the fourth quarter of 2021 compared to $13.2 million for the fourth quarter of 2020.
Total revenue was $1.5 million for the fourth quarter of 2021 compared to $1.6 million for the fourth quarter of 2020.
Research and development (R&D) expenses were $14.1 million for the quarter ended December 31, 2021 compared to $9.0 million for the prior year period.
The $5.1 million increase was the result of additional zunsemetinib expenses, including costs associated with clinical development activities for a Phase 2b trial for moderate to severe RA and a Phase 2 trial for moderate to severe HS and preclinical development activities related to ATI-2231.
General and administrative (G&A) expenses were $6.9 million for the quarter ended December 31, 2021 compared to $4.9 million for the prior year period.
The $2.0 million increase was primarily the result of higher compensation-related costs, including stock-based compensation, as well as higher accounting, compliance and professional fees. Severance payments relating to the retirement of our former Chief Legal Officer also contributed to the increase.
Revaluation of contingent consideration charges related to the Confluence acquisition was $2.2 million for the quarter ended December 31, 2021 compared to $0 for the prior year period.
Full Year 2021

Net loss was $90.9 million for the year ended December 31, 2021 compared to $51.0 million for the year ended December 31, 2020.
Total revenue was $6.8 million for the year ended December 31, 2021 compared to $6.5 million for the year ended December 31, 2020.
R&D expenses were $43.8 million for the year ended December 31, 2021 compared to $29.3 million for the prior year period.
The $14.5 million increase was primarily the result of additional zunsemetinib expenses, including costs associated with drug candidate development and clinical development activities for a Phase 2b trial for moderate to severe RA and a Phase 2a trial for moderate to severe HS. Continued investment in the further development of Aclaris’ immuno-inflammatory drug development pipeline also contributed to the increase as Aclaris progressed toward the October 2021 IND submission for ATI-2138 and began pre-clinical development activities on ATI-2231.
G&A expenses were $23.6 million for the year ended December 31, 2021 compared to $20.5 million for the prior year period.
The $3.1 million increase was primarily the result of higher stock-based compensation costs as well as higher accounting, compliance and professional fees. Severance payments relating to the retirement of our former Chief Legal Officer also contributed to the increase.
Revaluation of contingent consideration charges related to the Confluence acquisition was $24.3 million for the year ended December 31, 2021 compared to $2.4 million for the prior year period.